Inhaled nitric oxide prevents pulmonary endothelial dysfunction after mesenteric ischemia-reperfusion

David A. Fullerton, John H. Eisenach, Robert C. McIntyre, Randall S. Friese, Brett C. Sheridan, Gates B. Roe, Jeanette Agrafojo, Anirban Banerjee, Alden H. Harken

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27 Scopus citations

Abstract

This study examined the effect of inhaled nitric oxide (NO) on lung neutrophil accumulation and endothelial-dependent and -independent guanosine 3',5'-cyclic monophosphate (cGMP)-mediated mechanisms of pulmonary vasorelaxation after mesenteric ischemia-reperfusion (I/R) in mechanically ventilated rats. Inhaled NO (20 ppm) was administered in two protocols: 1) throughout mesenteric I/R and 2) during mesenteric reperfusion alone. Concentration-response curves were generated (10-9 to 10-6 M) for acetylcholine (ACh), A23187, and sodium nitroprusside (SNP) in isolated pulmonary arterial rings preconstricted with phenylephrine. Lung neutrophil accumulation [myeloperoxidase assay (MPO)] was significantly increased from 2.4 ± 0.2 units/g lung wt in controls to 10.3 ± 0.4 after 1 h of superior mesenteric artery occlusion and 2 h of reperfusion. Lung MPO activity was not different from controls in rats receiving inhaled NO either 1) during mesenteric I/R or 2) during mesenteric reperfusion alone. The concentration- response curves demonstrated significant impairment of pulmonary vasorelaxation by endothelial-dependent mechanisms (response to ACh and A23187) but not endothelial-independent pulmonary vasorelaxation (response to SNP) after mesenteric I/R. This pulmonary vasomotor dysfunction was prevented by administration of inhaled NO during either mesenteric I/R or during mesenteric reperfusion alone. We conclude that inhaled NO prevents lung neutrophil accumulation and pulmonary vascular endothelial dysfunction after mesenteric I/R.

Original languageEnglish (US)
Pages (from-to)L326-L331
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume271
Issue number2 15-2
DOIs
StatePublished - Aug 1996

Keywords

  • A23187
  • acetylcholine
  • guanosine 3',5'-cyclic monophosphate
  • neutrophil
  • pulmonary vascular endothelium
  • smooth muscle
  • sodium nitroprusside

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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